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The macrolide-specific pump MacAB, the only ABC-type drug efflux pump in\n                    <jats:italic>Salmonella<\/jats:italic>\n                    , has previously been linked to virulence in mice. The molecular mechanism of this link between\n                    <jats:italic>macAB<\/jats:italic>\n                    and infection is unclear. We demonstrate that\n                    <jats:italic>macAB<\/jats:italic>\n                    plays a role in the detoxification of reactive oxygen species (ROS), compounds that salmonellae are exposed to at various stages of infection.\n                    <jats:italic>macAB<\/jats:italic>\n                    is induced upon exposure to H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and is critical for survival of\n                    <jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>\n                    serovar\u00a0Typhimurium in the presence of peroxide. Furthermore, we determined that\n                    <jats:italic>macAB<\/jats:italic>\n                    is required for intracellular replication inside J774.A1 murine macrophages but is not required for survival in ROS-deficient J774.D9 macrophages.\n                    <jats:italic>macAB<\/jats:italic>\n                    mutants also had reduced survival in the intestine in the mouse colitis model, a model characterized by a strong neutrophilic intestinal infiltrate where bacteria may experience the cytotoxic actions of ROS. Using an Amplex red-coupled assay,\n                    <jats:italic>macAB<\/jats:italic>\n                    mutants appear to be unable to induce protection against exogenous H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:italic>in vitro<\/jats:italic>\n                    , in contrast to the isogenic wild type. In mixed cultures, the presence of the wild-type organism, or media preconditioned by the growth of the wild-type organism, was sufficient to rescue the\n                    <jats:italic>macAB<\/jats:italic>\n                    mutant from peroxide-mediated killing. Our data indicate that the MacAB drug efflux pump has functions beyond resistance to antibiotics and plays a role in the protection of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    against oxidative stress. Intriguingly, our data also suggest the presence of a soluble anti-H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    compound secreted by\n                    <jats:italic>Salmonella<\/jats:italic>\n                    cells through a MacAB-dependent mechanism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The ABC-type multidrug efflux pump MacAB is known to be required for\n                    <jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>\n                    serovar Typhimurium virulence after oral infection in mice, yet the function of this pump during infection is unknown. We show that this pump is necessary for colonization of niches in infected mice where salmonellae encounter oxidative stress during infection. MacAB is required for growth in cultured macrophages that produce reactive oxygen species (ROS) but is not needed in macrophages that do not generate ROS. In addition, we show that MacAB is required to resist peroxide-mediated killing\n                    <jats:italic>in vitro<\/jats:italic>\n                    and for the inactivation of peroxide in the media. Finally, wild-type organisms, or supernatant from wild-type organisms grown in the presence of peroxide, rescue the growth defect of\n                    <jats:italic>macAB<\/jats:italic>\n                    mutants in H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    . MacAB appears to participate in the excretion of a compound that induces protection against ROS-mediated killing, revealing a new role for this multidrug efflux pump.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00630-13","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T23:20:48Z","timestamp":1383088848000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":106,"title":["The ABC-Type Efflux Pump MacAB Protects Salmonella enterica serovar Typhimurium from Oxidative Stress"],"prefix":"10.1128","volume":"4","author":[{"given":"Lydia M.","family":"Bogomolnaya","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&amp;M University System Health Science Center, Bryan, Texas, USA"},{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine D.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&amp;M University System Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Talamantes","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&amp;M University System Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"Maple","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&amp;M University System Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury","family":"Ragoza","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&amp;M University System Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Vazquez-Torres","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, University of Colorado at Denver, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Andrews-Polymenis","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&amp;M University System Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(01)01495-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196909182811202"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-114-3-195"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.65.6.1125"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/168.5.1304"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","unstructured":"SirinavinS\nGarnerP\n. 2000. 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